Cultured mammalian cells are the most commonly used model organisms, both in academic and in industrial biology. However, the tools that are available for manipulating these cells have been relatively primative compared to those available in other model organisms, such as C. elegans and Drosophila. It has been the primary mission of Genetica to develop technologies that improve the ability to manipulate mammalian cells in culture. A collateral benefit of such studies will also be improved technologies to manipulate mammalian model organisms. Genetica has developed a suite of tools, the MaRX system, which enable forward genetics to be harnessed to address numerous biological problems in cell culture. However, to date, we have most often used this system for rescue of phenotypes by ectopic expression. The goal of this proposal is to develop the ability to use double-stranded RNA-induced gene silencing (RNAi) as a tool for stable suppression of gene function in mammalian cells. This goal is strongly rooted in promising preliminary data that predicts the ultimate success of this endeavor. Such success would revolutionize the ability of investigators studying mammalian cells to determine gene function and would thus have profound affects on the identification and validation of potential therapeutic targets. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE